Citalopram is a well-known antidepressant drug and is chemically known as 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile. It is a selective, centrally acting serotonin (5-hydroxytryptamine; S-HT) reuptake inhibitor, accordingly having antidepressant activities.
Citalopram was first disclosed in a German patent DE 2,657,013, corresponding to U.S. Pat. No. 4,136,193. A process for preparation of citalopram from the corresponding 5-bromo-derivative by reaction with cuprous cyanide in a suitable solvent and by alkylation of 5-bromo-phtalane is disclosed in DE 2,657,013.
Escitalopram is a pure S-enantiomer (single isomer) of the racemic citalopram.

Escitalopram is at least 100 fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate and is widely used as an antidepressant.
Escitalopram and processes for its preparation were first disclosed in EP 347066. The failure of previous attempts to crystallize diastereomeric salts of citalopram enantiomers has been acknowledged in EP 347066. The aforementioned European patent discloses two processes which provide a solution to the problem of obtaining diastereomeric salts of citalopram enantiomers by employing a racemic diol compound of Formula A as a starting material.

In accordance with a first process as disclosed in EP 347066, the diol is reacted with an enantiomerically pure acid derivative, such as (+)- or (−)-α-methoxy-α-trifluoromethyl-phenylacetyl chloride to form a mixture of diastereomeric esters, which are separated by HPLC or fractional crystallization, whereupon the ester with the correct stereochemistry is enantioselectively converted into escitalopram.
In accordance with a second process as disclosed in EP 347066, the diol of Formula A is separated into the enantiomers by stereoselective crystallization with an enantiomerically pure acid such as (+)-di-p-toluoyltartaric acid, whereupon the S-enantiomer of the diol of the Formula I is enantioselectively converted to escitalopram.
Several other different processes for the preparation of escitalopram have been reported. However, all the hitherto reported processes for preparation of escitalopram employ a plurality of reagents and involve methods steps which make the overall processes uneconomical. Furthermore, the aforesaid reported processes do not give high purity enantiomers of citalopram. There is therefore a need for an economical process for the preparation of escitalopram that results in products in high yield with high purity.